We propose experiments to investigate the disturbances in feeding and locomotion in genetically obese mice (C57-Bl/6J-obob). We also plan to investigate the effects of three different therapies on the development of obesity in these mice. The therapies are abdominal vagotomy, chronic treatment with the synthetic C-terminal octapeptide of the intestinal hormone cholecystokinin (CCK-8) and chronic treatment with L-DOPA. We plan to use normal and ventromedial hypothalamic lesioned rats to analyze changes in the potency of preabsorptive satiety signals from the gastrointestinal tract when rats are eating larger and smaller meals than normal. Finally we plan to extend our analysis of the deficits in drinking after abdominal vagotomy in rats to determine the effect on these deficits of diurnal rhythm, intracranial administration of dipsogens and the effect of ventromedial hypothalamic lesions.